The focus of this project is the use of MRI to understand the pathophysiology of multiple sclerosis (MS) and to determine whether disease activity is altered by various immunomodulatory treatments such as Anti-Tac antibodies or Roliprom, a phosphodiesterase 4 inhibitor and to monitor the natural history of MS, Anti-Tac antibodies in combination with Interferon beta have resulted in improvement of clinical and MRI MS disease activity in patients that were previously considered non-responders to conventional therapy. A phase II trial is underway evaluating the new oral agent, Roliprom for the treatment of relapsing remitting MS patients using suppression of frequency of enhancing lesions as an outcome measure. Stage 1of this two part study has been completed in more advanced MS patients and there was no change or increase in the patients MRI disease activity. Enrollment has started of active early relapsing remitting MS patients into this study and changes in enhancing lesions compared to baseline disease activity will be used as primary outcome measure. Cerebral atrophy represents the summation of all ongoing macroscopic and microscopic pathologic processes including inflammation, demyelination, neuronal and axonal loss in patients with MS. MS patients have approximately 2-3 times increase in the rate of progression of cerebral atrophy compared to age matched healthy controls. Although high-resolution three-dimensional MRI techniques have been used to study cerebral atrophy in other central nervous diseases such as Alzheimers, these techniques have not been applied to the study of MS patients. Using standard clinical MRI examination for evaluating MS patients, there was a significant difference in the rate of progression of atrophy that was dependent on the MRI pulse sequence used or the image analysis algorithm used in 10 relapsing remitting MS patients. These results indicated that the rate of cerebral atrophy may progress at rates varying between 0.5 to 1.5% per year depending on which MR images were evaluated and indicate that standards need to be adopted if changes in the rate of progression of cerebral atrophy will be used as an outcome measure in clinical trials. In addition, we have reported a significant decrease in brain volume as a result of treatment with intravenous steroids for acute exacerbations in MS patients Prospective longitudinal studies are need to determine how measures of cerebral atrophy can be used to monitor treatment effects in individual MS patients.